Continued studies of experimental allergic encephalomyelitis (EAE) will focus on several events and determinants discovered during the preceeding period of grant support and shown to be of special immunopathogenetic importance in this prototypic autoimmune disease: 1) Role of circulating myelin basic protein (MBP) fragments in Lewis rats, especially those reacting with high or/and medium affinity MBP antibodies in RIA reagent antisera, in immunomodulating MBP-reactive host lymphoid clones will be studied in greater detail. 2) In extending work in Lewis rats implicating the clotting cascade in development of the neuroinjury characterizing EAE, specific serum proteases with the capacity to degrade MBP will be studied in Lewis rats in detail. 3) Characterization of soluble products derived from sensitized incubated lymph node cells of donor Lewis rats sensitized to spinal cord-adjuvant with the capacity to transfer typical lesions of EAE in syngeneic recipients will be a high priority in defining the nature of host effector immune responses initiating the neuroinjury of EAE. 4) Locus and mechanisms of the EAE-potentiating effect of whole body irradiation in Syrian hamsters and further study of the striking EAE-augmenting effect of Corynebacterium parvum in Lewis rats and other rodents known to be susceptible to EAE.